1. Field of the Invention
This invention relates to a novel fetal lung maturity test employing lamellar body solubilization and kits suitable for practicing the method of this invention.
Hyaline membrane disease is caused in part by inadequate lung cell synthesis of lamellar bodies (which contain surface-tension lowering material, surfactant). The neonatal hyaline membrane disease represents a major cause of perinatal mortality. It is therefore desirable to have a simple and rapid test which would permit a determination of lung maturity by determining lamellar body presence in amniotic fluid, the results of which would provide an indication of the neonatal pulmonary maturity. Desirably, the test should be simple, rapid and provides results that are easy to interpret.
2. Description of Prior Art
Several distinct methods exist for the assessment of fetal lung maturity. See Brown L. Duck-Chong C., "Methods of Evaluating Fetal Lung Maturity", CRC Critical Rev. in Clin. Lab. Sci. 16/2, 85-159 (1982).
The chromatographic measurement of phospholipid surfactants is time consuming, technically demanding, and fairly expensive. The "bubble" or foam stability index (U.S. Pat. No. 4,233,032) has potential for human error during the addition of the sample and human subjectivity in deciding a positive end point, i.e., what is a "stable foam". The "Amniostat" (U.S. Pat. Nos. 4,388,412 and 4,459,362), an immunological agglutination test suffers from the same drawbacks as the foam stability index. The OD.sub.650 test, M. Y. Tsai et al., Am. J. Obstet. Gynecol., 146:963, 1983, has the potential for nonspecific absorbance from nonsurfactant components of amniotic fluid. However, the result is less subject to human interpretation as compared with bubble and agglutination tests because it is read on a spectrophotometer.
From 1979 to 1982 Dr. Oulton published a series of articles demonstrating that amniotic fluid surfactant is present in globular-like structures which showed good correlation with fetal lung function. M. Oulton, Am. J. Obstet. Gynecol., 135:337, 1979; M. Oulton et al, Pediatr. Res., 14:722, 1980; and M. Oulton et al, Am. J. Obstet. Gynecol., 142:684, 1982. Dr. Oulton also characterized their content and development during gestational time. These data provide a sound theoretical basis for the concept of determining fetal lung maturity via the measurement of lamellar bodies.
Beginning in 1976 and more recently in 1983, Tsai et al, supra., the turbidity of amniotic fluid was used as an indicator of fetal lung maturity. The increasing turbidity during later stages of development is due to many factors, some of which include absorbance by small molecules, absorbance by large molecular structures and light scatter by macromolecular aggregates, including but not limited to lamellar bodies, and light scatter due to cells. Such nonspecificity, not to mention any due to contamination by other biological material, has caused mixed reviews among the clinical chemistry community.
One version of the subject invention has been described partially in the literature S. L. Weitz and J. R. Swanson, Clin. Chem., 31:951, June, 1985; and additional abstract data presented at the annual meeting of the American Association for Clinical Chemistry, Atlanta, Ga. July 21-26, 1985.